BACKGROUND A 70-year-old man with hepatitis C virus-related recurrent hepatocellular carcinoma was admitted for further diagnosis of a 1 cm iso-hyperechoic nodule in segment(S)5.CASE SUMMARY Gadolinium ethoxybenzyl di...BACKGROUND A 70-year-old man with hepatitis C virus-related recurrent hepatocellular carcinoma was admitted for further diagnosis of a 1 cm iso-hyperechoic nodule in segment(S)5.CASE SUMMARY Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging(EOB-MRI)revealed the nodule in S5 with a defect at the hepatobiliary phase,hyperintensity on diffusion weighted imaging(DWI)and hypointensity on apparent diffusion coefficient(ADC)map.Contrast-enhanced computed tomography revealed hypervascularity at the early phase,and delayed contrast-enhancement was observed at the late phase.Contrast-enhanced ultrasound(US)revealed incomplete defect at the late vascular phase.Inflammatory liver tumor,lymphoproliferative disease,intrahepatic cholangiocarcinoma(small duct type)and bile duct adenoma were suspected through the imaging studies.US guided biopsy,however,showed a noncaseating hepatic sarcoid-like epithelioid granuloma(HSEG),and histopathological analysis disclosed spindle shaped epithelioid cells harboring Langhans-type multinucleated giant cells.One month after admission,EOB-MRI signaled the disappearance of the defect at the hepatobiliary phase,of hyperintensity on DWI,of hypointensity on ADC map,and no stain at the early phase.CONCLUSION That the patient had received BNT162b2 messenger RNA(mRNA)coronavirus disease 2019 vaccination 3 mo before the occurrence of HSEG,and that its disappearance was confirmed 4 mo after mRNA vaccination suggested that the drug-induced sarcoidosis-like reaction(DISR)might be induced by the mRNA vaccination.Fortunately,rechallenge of drug-induced DISR with the third mRNA vaccination was not confirmed.展开更多
In 2024, COVID-19 vaccination became mandatory in Brazil for children aged 6 months to 4 years. The product available for this purpose is the BNT162b2 messenger RNA, whose potential risks are still not fully known com...In 2024, COVID-19 vaccination became mandatory in Brazil for children aged 6 months to 4 years. The product available for this purpose is the BNT162b2 messenger RNA, whose potential risks are still not fully known compared to those of immunizations based on other platforms. This study assessed the current short term benefit/risk of BNT162b2 in pediatric population as a basis for discussion about the mandatory use or the freedom of choice on mRNA products in this age group. Methods. The epidemiology of severe acute respiratory syndrome was evaluated in Brazil based on freely available public data in the years 2022 and 2023, in children aged 6 months to 4 years. Results. The number needed to treat (NNT) with BNT162b2 to prevent one death from COVID-19 in this age group ranged from 208,856 to 548,246. The number needed to harm (NNH) of vaccine-associated death can range from 42,373 to 909,090. Conclusions. The results of this study indicate a borderline short-term benefit/risk balance of the BNT162b2 vaccine for the Brazilian population aged 6 months to 4 years. In this scenario, free informed choices regarding the use of mRNA products should be guaranteed for all.展开更多
Since the commercialization of the frst liposomes used for drug delivery,Doxil/Caelyx® and Myocet®,tremendous progress has been made in understanding interactions between nanomedicines and biological systems...Since the commercialization of the frst liposomes used for drug delivery,Doxil/Caelyx® and Myocet®,tremendous progress has been made in understanding interactions between nanomedicines and biological systems.Fundamental work at the interface of engineering and medicine has allowed nanomedicines to deliver therapeutic small molecules and nucleic acids more effciently.While nanomedicines are used in oncology for immunotherapy or to deliver combinations of cytotoxics,the clinical successes of gene silencing approaches like patisiran lipid complexes(Onpattro®)have paved the way for a variety of therapies beyond cancer.In parallel,the global severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)pandemic has highlighted the potential of mR NA vaccines to develop immunization strategies at unprecedented speed.To rationally design therapeutic and vaccines,chemists,materials scientists,and drug delivery experts need to better understand how nanotechnologies interact with the immune system.This review presents a comprehensive overview of the innate and adaptative immune systems and emphasizes the intricate mechanisms through which nanomedicines interact with these biological functions.展开更多
Background:Data on the immunogenicity and safety of heterologous immunization schedules are inconsistent.This study aimed to evaluate the immunogenicity and safety of homologous and heterologous immunization schedules...Background:Data on the immunogenicity and safety of heterologous immunization schedules are inconsistent.This study aimed to evaluate the immunogenicity and safety of homologous and heterologous immunization schedules.Methods:Multiple databases with relevant studies were searched with an end date of October 31,2021,and a website including a series of Coronavirus disease 2019 studies was examined for studies before March 31,2022.Randomized controlled trials(RCTs)that compared different heterologous and homologous regimens among adults that reported immunogenicity and safety outcomes were reviewed.Primary outcomes included neutralizing antibodies against the original strain and serious adverse events(SAEs).A network meta-analysis(NMA)was conducted using a random-effects model.Results:In all,11 RCTs were included in the systematic review,and nine were ultimately included in the NMA.Among participants who received two doses of CoronaVac,another dose of mRNA or a non-replicating viral vector vaccine resulted in a significantly higher level of neutralizing antibody than a third CoronaVac 600 sino unit(SU);a dose of BNT162b2 induced the highest geometric mean ratio(GMR)of 15.24,95%confidence interval[CI]:9.53–24.39.Following one dose of BNT162b2 vaccination,a dose of mRNA-1273 generated a significantly higher level of neutralizing antibody than BNT162b2 alone(GMR=1.32;95%CI:1.06–1.64),NVX-CoV2373(GMR=1.60;95%CI:1.16–2.21),or ChAdOx1(GMR=1.80;95%CI:1.25–2.59).Following one dose of ChAdOx1,a dose of mRNA-1273 was also more effective for improving antibody levels than ChAdOx1(GMR=11.09;95%CI:8.36–14.71)or NVX-CoV2373(GMR=2.87;95%CI:1.08–3.91).No significant difference in the risk for SAEs was found in any comparisons.Conclusions:Relative to vaccination with two doses of CoronaVac,a dose of BNT162b2 as a booster substantially enhances immunogenicity reactions and has a relatively acceptable risk for SAEs relative to other vaccines.For primary vaccination,schedules including mRNA vaccines induce a greater immune response.However,the comparatively higher risk for local and systemic adverse events introduced by mRNA vaccines should be noted.Registration:PROSPERO;https://www.crd.york.ac.uk/PROSPERO/;No.CRD42021278149.展开更多
文摘BACKGROUND A 70-year-old man with hepatitis C virus-related recurrent hepatocellular carcinoma was admitted for further diagnosis of a 1 cm iso-hyperechoic nodule in segment(S)5.CASE SUMMARY Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging(EOB-MRI)revealed the nodule in S5 with a defect at the hepatobiliary phase,hyperintensity on diffusion weighted imaging(DWI)and hypointensity on apparent diffusion coefficient(ADC)map.Contrast-enhanced computed tomography revealed hypervascularity at the early phase,and delayed contrast-enhancement was observed at the late phase.Contrast-enhanced ultrasound(US)revealed incomplete defect at the late vascular phase.Inflammatory liver tumor,lymphoproliferative disease,intrahepatic cholangiocarcinoma(small duct type)and bile duct adenoma were suspected through the imaging studies.US guided biopsy,however,showed a noncaseating hepatic sarcoid-like epithelioid granuloma(HSEG),and histopathological analysis disclosed spindle shaped epithelioid cells harboring Langhans-type multinucleated giant cells.One month after admission,EOB-MRI signaled the disappearance of the defect at the hepatobiliary phase,of hyperintensity on DWI,of hypointensity on ADC map,and no stain at the early phase.CONCLUSION That the patient had received BNT162b2 messenger RNA(mRNA)coronavirus disease 2019 vaccination 3 mo before the occurrence of HSEG,and that its disappearance was confirmed 4 mo after mRNA vaccination suggested that the drug-induced sarcoidosis-like reaction(DISR)might be induced by the mRNA vaccination.Fortunately,rechallenge of drug-induced DISR with the third mRNA vaccination was not confirmed.
文摘In 2024, COVID-19 vaccination became mandatory in Brazil for children aged 6 months to 4 years. The product available for this purpose is the BNT162b2 messenger RNA, whose potential risks are still not fully known compared to those of immunizations based on other platforms. This study assessed the current short term benefit/risk of BNT162b2 in pediatric population as a basis for discussion about the mandatory use or the freedom of choice on mRNA products in this age group. Methods. The epidemiology of severe acute respiratory syndrome was evaluated in Brazil based on freely available public data in the years 2022 and 2023, in children aged 6 months to 4 years. Results. The number needed to treat (NNT) with BNT162b2 to prevent one death from COVID-19 in this age group ranged from 208,856 to 548,246. The number needed to harm (NNH) of vaccine-associated death can range from 42,373 to 909,090. Conclusions. The results of this study indicate a borderline short-term benefit/risk balance of the BNT162b2 vaccine for the Brazilian population aged 6 months to 4 years. In this scenario, free informed choices regarding the use of mRNA products should be guaranteed for all.
基金the financial support of the Canadian agencies Natural Sciences and Engineering Research Council of Canada,the Canada Foundation for Innovation,and the Fondation du CHU de Quebec。
文摘Since the commercialization of the frst liposomes used for drug delivery,Doxil/Caelyx® and Myocet®,tremendous progress has been made in understanding interactions between nanomedicines and biological systems.Fundamental work at the interface of engineering and medicine has allowed nanomedicines to deliver therapeutic small molecules and nucleic acids more effciently.While nanomedicines are used in oncology for immunotherapy or to deliver combinations of cytotoxics,the clinical successes of gene silencing approaches like patisiran lipid complexes(Onpattro®)have paved the way for a variety of therapies beyond cancer.In parallel,the global severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)pandemic has highlighted the potential of mR NA vaccines to develop immunization strategies at unprecedented speed.To rationally design therapeutic and vaccines,chemists,materials scientists,and drug delivery experts need to better understand how nanotechnologies interact with the immune system.This review presents a comprehensive overview of the innate and adaptative immune systems and emphasizes the intricate mechanisms through which nanomedicines interact with these biological functions.
基金National Key R&D Program of China(No.2021YFC2301601)
文摘Background:Data on the immunogenicity and safety of heterologous immunization schedules are inconsistent.This study aimed to evaluate the immunogenicity and safety of homologous and heterologous immunization schedules.Methods:Multiple databases with relevant studies were searched with an end date of October 31,2021,and a website including a series of Coronavirus disease 2019 studies was examined for studies before March 31,2022.Randomized controlled trials(RCTs)that compared different heterologous and homologous regimens among adults that reported immunogenicity and safety outcomes were reviewed.Primary outcomes included neutralizing antibodies against the original strain and serious adverse events(SAEs).A network meta-analysis(NMA)was conducted using a random-effects model.Results:In all,11 RCTs were included in the systematic review,and nine were ultimately included in the NMA.Among participants who received two doses of CoronaVac,another dose of mRNA or a non-replicating viral vector vaccine resulted in a significantly higher level of neutralizing antibody than a third CoronaVac 600 sino unit(SU);a dose of BNT162b2 induced the highest geometric mean ratio(GMR)of 15.24,95%confidence interval[CI]:9.53–24.39.Following one dose of BNT162b2 vaccination,a dose of mRNA-1273 generated a significantly higher level of neutralizing antibody than BNT162b2 alone(GMR=1.32;95%CI:1.06–1.64),NVX-CoV2373(GMR=1.60;95%CI:1.16–2.21),or ChAdOx1(GMR=1.80;95%CI:1.25–2.59).Following one dose of ChAdOx1,a dose of mRNA-1273 was also more effective for improving antibody levels than ChAdOx1(GMR=11.09;95%CI:8.36–14.71)or NVX-CoV2373(GMR=2.87;95%CI:1.08–3.91).No significant difference in the risk for SAEs was found in any comparisons.Conclusions:Relative to vaccination with two doses of CoronaVac,a dose of BNT162b2 as a booster substantially enhances immunogenicity reactions and has a relatively acceptable risk for SAEs relative to other vaccines.For primary vaccination,schedules including mRNA vaccines induce a greater immune response.However,the comparatively higher risk for local and systemic adverse events introduced by mRNA vaccines should be noted.Registration:PROSPERO;https://www.crd.york.ac.uk/PROSPERO/;No.CRD42021278149.
